Analysis of a novel human protein WDC146 highly expressed in testis : for elucidation of the function during spermatogenesis

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1) WDC146 is a novel human protein of 146 kDa which is expressed highly in testis. It is composed of three domains, a WD40 domain, a collagen-like domain and a GPR-rich repeat domain, from N-terminus to C-terminus, respectively.2) WDC146 is highly expressed in testis both in human and mouse. The amino acid sequence showed significant homology between them overall (96%), including complete match (100%) for the region of WD40 domain. Even in Drosophila and yeast, we identified the sequence conserved in part.3) WDC146 showed marked expression in pachytene spermatocytes, and nuclear and perinuclear localization was observed intracellularly.4) The detailed analysis of the expression pattern of WDC146 during spermatogenesis is in progress, with the technical difficulty of fixation of testis applicable for in situ hybrization.5) WD40 domain is known to work as the platform motif as the time of protein-protein interaction. The two-hybrid screening was executed repeatedly to detect interactive protein with WDC146, but not yet succeed.6) Cancer-testis genes are defined as testis-specific genes also expressed in many tumors and tumor cell lines. WDC146 may be classified in them, as tumor cell lines tested all showed moderate expression of WDC146, though some tumors did not.7) The WDC146 gene is mapped at 2q14-21 and consists of 22 exons. Besides the intact mRNA of about 4kb, a chimeric one result from mis-splicing always detected at about 1kb size.8) The promoter region was identified within 0.5kb upstream region of exon 1.